# Molecular Mechanisms that Initiate Apical Dendrite Development During Embryonic Neuronal Development

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $392,024

## Abstract

Molecular mechanisms that initiate leading process and apical dendrite polarization
 during embryonic neuronal development
An early and essential event in mammalian embryonic brain development is neuronal polarization, in which distinct
axonal and dendritic compartments are formed. Axons and dendrites inherently differ in the molecular composition
of their cytoplasm, cytoskeleton, and plasma membrane. These differences underlie the unique morphology and
function of these compartments, and are responsible for directed information flow in the brain. Aberrations in neuron
polarization lead to developmental neuropathologies, intellectual disability, epilepsy, autism spectrum disorders, and
neuropsychiatric pathologies. Bipolar polarity establishment in postmitotic neocortical and hippocampal CA1
pyramidal neuron progenitors marks polarization of the axon and the apical dendrite. The apical dendrite will
develop from the leading process of the bipolar neuron whereas the trailing process will become the axon.
Specification of the axon has dominated studies on neuron polarization, yielding an understanding of the
mechanisms underlying axonal identity, its specification and growth. Much effort has also been directed towards
elucidation of the mechanisms that control later events in dendrite morphogenesis - growth, branching, and structural
plasticity. However, the events leading to bipolar polarity and the subsequent development of the apical dendrite,
have remained elusive. We propose that distinctly higher cyclic GMP (cGMP) generated via localized assembly of a
cGMP production machinery at the leading edge of developing pyramidal neurons, promotes bipolar polarity,
leading process formation, and apical dendrite development. Using state of the art lifetime decay FLIM-FRET
cGMP measurements in mouse developing pyramidal neurons in acute slice, combined with cutting edge genetic
manipulations, and localized, directed optogenetic manipulations of cGMP production, this study is designed to
determine the spatio-temporal regulation of cGMP during polarity establishment and apical dendrite development,
and to identify its mechanistic basis in developing pyramidal neurons in vivo. Our studies will provide important
advance in the understanding of the early molecular events that take place during axon and apical dendrite
establishment in principal excitatory neurons in the rodent brain, and will contribute to the identification of
molecular targets and development of therapeutics for developmental neuropathologies resulting from abnormal
axon and dendrite development.

## Key facts

- **NIH application ID:** 10428460
- **Project number:** 5R01NS119512-02
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Maya Shelly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,024
- **Award type:** 5
- **Project period:** 2021-06-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428460

## Citation

> US National Institutes of Health, RePORTER application 10428460, Molecular Mechanisms that Initiate Apical Dendrite Development During Embryonic Neuronal Development (5R01NS119512-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10428460. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*